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AIDS Care: Psychological and Socio-medical Aspects of AIDS/HIV Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/caic20 Trial participation disclosure and gel use behavior in the CAPRISA 004 tenofovir gel trial Stacey M. Succopa, Kathleen M. MacQueena, Francois van Loggerenbergb, Nelisile Majolab, Quarraisha Abdool Karimb & Salim S. Abdool Karimb a Social and Behavioral Health Sciences, FHI 360, Durham, NC, USA b Centre for the AIDS Program of Research in South Africa (CAPRISA), Durban, South Africa Published online: 06 Oct 2014.

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To cite this article: Stacey M. Succop, Kathleen M. MacQueen, Francois van Loggerenberg, Nelisile Majola, & Salim S. Abdool Karim (2014) Trial participation disclosure and gel use behavior in the CAPRISA 004 tenofovir gel trial, AIDS Care: Psychological and Socio-medical Aspects of AIDS/HIV, 26:12, 1521-1525, DOI: 10.1080/09540121.2014.938014 To link to this article: http://dx.doi.org/10.1080/09540121.2014.938014

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Trial participation disclosure and gel use behavior in the CAPRISA 004 tenofovir gel trial

Stacey M. Succopa*, Kathleen M. MacQueena, Francois van Loggerenbergb, Nelisile Majolab, Quarraisha Abdool Karimb and Salim S. Abdool Karimb

aSocial and Behavioral Health Sciences, FHI 360, Durham, NC, USA; bCentre for the AIDS Program of Research in South Africa (CAPRISA), Durban, South Africa (Received 14 November 2013; accepted 20 June 2014)

Disclosure, or open communication, by female microbicide trial participants of their trial participation and use of an investigational HIV prevention drug to a sexual partner may affect participants’ trial product usage behavior and contribute to poor adherence. With mixed results from recent microbicide clinical trials being linked to differing participant adherence, insights into the communication dynamics between trial participants and their sexual partners are particularly important. We examined the quantitative association between (1) communication of trial participation to a partner and participant adherence to gel and (2) communication of trial participation to a partner and participant HIV status. An in-depth adherence and product acceptability assessment was administered to the women participating in the CAPRISA 004 trial. Additionally, we collected qualitative data related to communication of trial participation and gel use. Qualitatively, among 165 women who had reported that they had discussed trial participation with others, most (68%) stated that they communicated participation to their sexual partner. Most of the women who had communicated study participation with their partners had received a positive/neutral response from their partner. Some of these women stated that gel use was easy; only a small number said that gel use was difficult. Among women who did not communicate their study participation to their partners, difficulty with gel use was more common and some women stated that they feared communicating their participation. Quantitatively, there was no statistically significant difference in the proportions of women who had communicated study participation to a partner across different adherence levels or HIV status. A deeper knowledge of the dynamics surrounding trial participation communication to male partners will be critical to understanding the spectrum of trial product usage behavior, and ultimately to designing tailored strategies to assist trial participants with product adherence. Keywords: ; HIV prevention; disclosure; adherence; covert use; partner dynamics

Introduction Study product adherence has been cited as an import- Previous microbicide, diaphragm, and studies and ant factor in the mixed results seen in recent antiretroviral clinical trials have explored barriers women face in (ARV)-based microbicide and HIV prevention trials. The disclosing, or openly communicating, study or trial parti- 2010 CAPRISA 004 tenofovir gel microbicide trial in cipation to sexual partners including fear of violating trust South Africa demonstrated a 39% reduction in HIV ’ infections; in secondary analyses, infections were reduced

Downloaded by [5.249.37.136] at 01:47 03 March 2015 or relationship norms, partners refusal of study product use, and physical violence (Gafos et al., 2012; Montgomery by 54% among women with high adherence to the study et al., 2008;Montgomery,Gafosetal.,2010; Montgomery, product (Abdool Karim et al., 2010). Similar dose– Cheng et al., 2010;Morrowetal.,2003; Sahin-Hodoglugil responseeffectshavebeenobservedinotherHIVpreven- et al., 2006; Sahin-Hodoglugil et al., 2011; Woodsong & tion trials including iPrEx (Grant et al., 2010), Partner- Alleman, 2008; Woodsong et al., 2013). Studies have also sPrep (Baeten et al., 2012), and TDF2 (Thigpen et al., explored linkages between communication of participation 2011). In contrast, two studies with evidence of poor and study product adherence and found more consistent adherence were unable to demonstrate product effective- usage among women whose partners knew of their ness (Marrazzo, Ramjee, & Nair, 2013;VanDamme participation (Greene et al., 2010; Montgomery et al., 2008; Montgomery, Gafos et al., 2010; Montgomery, et al., 2012). Cheng et al., 2010; Pistorius et al., 2004; van der Straten We used a mixed methods approach to explore the et al., 2008; Woodsong & Alleman, 2008). One study relationships between communication of participation showed product adherence was more difficult for women in the CAPRISA 004 microbicide trial to male sexual whose partners were not aware of their participation and partners, participant HIV status, and use of study product use (Sahin-Hodoglugil et al., 2006). product.

*Corresponding author. Email: [email protected]

This material is published by permission of the U.S. Agency for International Development (USAID) for the US Department of Energy under Contract No. [GHO‑A‑00‑09‑00016-00]. The US Government retains for itself, and others acting on its behalf, a paid-up, non-exclusive, and irrevocable worldwide license in said article to reproduce, prepare derivative works, distribute copies to the public, and perform publicly and display publicly, by or on behalf of the Government. This is an Open Access article. Non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly attributed, cited, and is not altered, transformed, or built upon in any way, is permitted. The moral rights of the named author(s) have been asserted. 1522 S.M. Succop et al.

Methods participants’ HIV status. However, 10 participants (with positive HIV test results) divulged their HIV test results The study was approved by FHI 360’s Protection of during the interview. Human Subjects Committee in Durham, NC, USA and the University of KwaZulu-Natal Biomedical Research Ethics Committee in Durban, South Africa. Data analysis Logistic regression was used to assess the association between communication of trial participation to a partner Study population and (1) participant adherence to gel and (2) participant This study was conducted simultaneously with the HIV status. CAPRISA 004 microbicide gel in KwaZulu- Qualitative data were coded using a team-based, Natal, South Africa. Participants (n = 277) were recruited data-driven, thematic approach and implemented with from the CAPRISA 004 study population (n =889).All AnSWR qualitative data analysis software. Two coders trial participants with a positive HIV test result at their separately coded 20% of transcripts and inter-coder 1 monthly clinic visit were targeted for recruitment and 72 agreement checks were conducted. Discrepancies in confirmed positive were enrolled. Trial participants with coding were resolved to ensure a minimum of 80% negative HIV test results were selected randomly (n = agreement. Code frequencies and co-occurrences were 205). Demographics and sexual behavior were similar to examined for trends related to trial participation com- the larger CAPRISA 004 cohort. A detailed description of munication, ease of gel use, and partner’s reaction to the study design has been published elsewhere (MacQueen communication of trial participation. et al., 2014). All participants previously met CAPRISA 004 trial eligibility criteria (aged 18–40 years, sexually active, Results HIV-negative at enrollment, not pregnant, and using a Quantitative findings non-barrier form of contraception). Additionally, women Participant demographics and baseline sexual behavior had to be enrolled in the trial for a minimum of two data are shown in Table 1. Logistic regression analyses months and not be suspended from gel use for three examining the degree to which communication with a months prior to their most recent HIV test. partner predicted adherence level or HIV status failed to reveal any statistically significant associations (Table 2). Data collection A one-time, face-to-face in-depth adherence and gel Qualitative findings acceptability assessment was conducted with participants In total, 165 (60%) participants discussed communication in the local language, isiZulu. Topics covered included: of trial participation during their interview. Of these, most . general feelings about trial participation; (68%) stated that they had communicated participation in . gel and condom use patterns and challenges; the trial to at least one sexual partner. A majority of the

Downloaded by [5.249.37.136] at 01:47 03 March 2015 . communication with others about the trial; communicators (n = 74, 65%) said their partners responded . community perceptions about the trial; and positively or neutrally. Some (n =23)saidgelusewas . beliefs about the gel. easy; only seven described gel use as difficult. Women reporting positive or neutral partners mentioned the ease of The Timeline Followback (TLFB) method (Carey, Carey, being able to insert gel in their partner’spresenceand Maisto, Gordon, & Weinhardt, 2001) was used to ability to use gel when their partner visited unexpectedly. measure gel usage over a three-month recall period. Some women said their partners facilitated use by provid- Adherence was measured by the proportion of vaginal ing reminders for gel insertion before and after sex and for sex events covered by the prescribed dosage of gel with trial-related appointments: 0–50% events covered categorized as low, 51–80% as moderate, and 81–100% as high. Prescribed dosage was Interviewer: Ok, is it difficult to remember to insert the gel? one dose within 12 hours before sex, one dose within 12 Respondent: No, it’s not difficult … Because anyway hours after sex, and no more than two doses in 24 hours I keep my gel where we sleep, then he also reminds me (Abdool Karim et al., 2010). Recorded interviews were because he is not someone with a good behavior so that transcribed by native isiZulu speakers using a standar- I get protected from getting the disease. dized transcription protocol (McLellan-Lemal, 2008) then translated into English. To reduce bias, measures Of the 165 women who discussed trial participation were taken to prevent interviewers from knowing communication, 52 (32%) did not communicate trial AIDS Care 1523

Table 1. Participant demographics and baseline sexual behavior.

Variable HIV+ participants (n = 72) HIV– participants (n = 205) Demographic characteristics Mean age (years) 22.7 24.2 Monthly income

participation to any partner. One-third of non-communica- incite anger from or lead to abandonment by their tors said that gel use was hard and more than 20% said partners or that their partners may prohibit gel use: they were afraid to communicate. Non-communicators said “ they were often unable to use gel when their partner was Respondent: One time my boyfriend asked me why am I feeling something water-like in your vagina? Do you present or when their partner visited unexpectedly: maybe have any disease or you have slept with someone ‘ ’ ’ ” Interviewer: What maybe made you not use the gel even else? I said, no, I don t have anything . Then he was a when you had sex? bit angry. Respondent: At other times it’s because you think this Interviewer: Why are you not telling him that you are person isn’t coming, you see, all of a sudden, you see using the gel? him arriving, then it’s not easy for me to insert this thing Respondent: No, he would be angry and tell me to stop. because he doesn’t know that I am using this gel. Two additional themes emerged among women who did They also expressed concern that they would be unable not communicate trial participation to any partner: (1) to hide the product and feared their partner would feel fear that communication would lead to their partner no the cold and wetness of the gel, which may cause longer using and (2) partial communication of arguments or accusations of cheating. Furthermore, some trial participation. The latter was discussed in two ways: said that communication of trial participation would some women communicated their participation in a Downloaded by [5.249.37.136] at 01:47 03 March 2015 Table 2. Results of regression analyses.

Adherence level regressed on communication with a partner

Adherence level Cumulative logistic regression

Communication with partner Participants (n = 271) Low Moderate High OR Lower → higher No 63 (23%) 14% 33% 52% 1.04 Yes 208 (77%) 14% 35% 51% [95% CI: 0.606, 1.783]

HIV status regressed on communication with a partner

HIV Logistic regression

Communication with partner Participants (n = 277) No Yes OR

No 67 (24%) 73% 27% 0.94 Yes 210 (76%) 74% 26% [95% CI: 0.506, 1.756] 1524 S.M. Succop et al.

clinical trial, but did not specify they were inserting a Acknowledgments microbicide into their vagina, while other women This work is made possible by the generous support of the revealed to their partner that they were participating in American people through the US Agency for International a trial that involved gel use, but did not specify the gel Development (USAID). was being studied for HIV prevention:

Respondent: I told him that I am cleaning my bladder, I Funding didn’t tell him it’s [the gel] purpose. Financial assistance was provided by USAID to FHI 360 under the terms of the Preventive Technologies Agreement [grant number GHO-A-00-09-00016-00]. The contents do not neces- sarily reflect the views of USAID or the US Government. Discussion The results described here add to the body of knowledge around partner communication in the context of an HIV Note prevention clinical trial and provide important insights 1. For more details about a description of the HIV testing into women’s successes and challenges adhering to algorithm, see Abdool Karim et al. (2010). microbicide gel. In the high HIV prevalence setting of KwaZulu-Natal, South Africa, the majority of study References participants communicated to their sexual partners that Abdool Karim, Q., Abdool Karim, S. S., Frohlich, J. A., Grobler, they were taking part in a microbicide trial. The A. C., Baxter, C., Mansoor, L. E., … Taylor, D. (2010). qualitative data showed that an important minority of Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. participants did not communicate their study participa- Science, 329,1168–1174. doi:10.1126/science.1193748 tion to their sexual partner(s), and many of these women Baeten, J. M., Donnell, D., Ndase, P., Mugo, N. R., Campbell, also reported difficulties with gel use. We did not find a J. D., Wangisi, J., … Celum, C. (2012). Antiretroviral statistically significant association between communica- prophylaxis for HIV prevention in heterosexual men and tion of trial participation and either study product women. New England Journal of Medicine, 367, 399–410. adherence or HIV status. However, an analysis of data Carey, M. P., Carey, K., Maisto, S., Gordon, C., & Weinhardt, L. from all participants interviewed when exiting the (2001). Assessing sexual risk behaviour with the Timeline CAPRISA 004 trial found a statistically significant Followback (TLFB) approach: Continued development and psychometric evaluation with psychiatric outpatients. though moderate relationship between disclosure and International Journal of STD & AIDS, 12, 365–375. adherence; no relationship was found between disclosure doi:10.1258/0956462011923309 and either HIV incidence or gel efficacy (Mngadi et al., Gafos, M., Mzimela, M., Ndlovu, H., Pool, R., Elford, J., & the 2014). Given the moderate association with adherence, it MDP Team. (2012). What have men got to do with it?: is possible that our sample size was too small to detect a The role of men in reproductive and sexual health in a relationship, or that it was obscured by biases in the self- predominantly rural area of KwaZulu-Natal, South Africa. report measures we used. Paper presented at the 2012 International Microbicides Conference, Sydney, Australia. Downloaded by [5.249.37.136] at 01:47 03 March 2015 This study adds to existing evidence concerning the Grant, R. M., Lama, J. R., Anderson, P. L., McMahan, V., Liu, important role that communication between partners can A. Y., Vargas, L., … Glidden, D. V. (2010). Preexposure play in supporting the use of products like tenofovir gel chemoprophylaxis for HIV prevention in men who have to reduce HIV acquisition in women. Just as importantly, sex with men. New England Journal of Medicine, 363, it highlights the importance of finding ways to support 2587–2599. doi:10.1056/NEJMoa1011205 product adherence among women who are not able to Greene, E., Batona, G., Hallad, J., Johnson, S., Neema, S., & communicate effectively with their partners about HIV Tolley, E. E. (2010). Acceptability and adherence of a candidate microbicide gel among high-risk women in Africa prevention. No single product adherence strategy can be and India. Culture, Health & Sexuality, 12,739–754. applied to all HIV prevention trials or product introduc- doi:10.1080/13691051003728599 tion campaigns. Guidance is needed to inform adherence MacQueen, K. M., Weaver, M. A., van Loggerenberg, F., strategies that both involve male partners of those Succop, S., Majola, N., Taylor, D., … Karim, S. A. women who want to communicate their study participa- (2014). Assessing adherence in the CAPRISA 004 tion and that support women who would like to use a tenofovir gel HIV prevention trial: Results of a nested – – study product without their partner’s knowledge. Moving case control study. AIDS and Behavior, 18, 826 832. forward, we must continue to monitor how communica- doi:10.1007/s10461-014-0753-8 ’ Marrazzo, J., Ramjee, G., & Nair, G. (2013). Pre-exposure tion dynamics with partners influence trial participants prophylaxis for HIV in women: Daily oral tenofovir, oral ability to adhere to microbicides and other new HIV tenofovir/emtricitabine or vaginal tenofovir gel in the prevention technologies like PrEP. VOICE study (MTN 003). Paper presented at the 20th AIDS Care 1525

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